title: Early initiation of gonadotropin-releasing hormone antagonist treatment results in a more stable endocrine milieu during the mid- and late-follicular phases: a randomized controlled trial comparing gonadotropin-releasing hormone antagonist initiation on cycle day 2 or 6.
abstract: OBJECTIVE
  To compare the effect of initiating GnRH antagonist (GnRH-a) on cycle day (CD) 2 vs. CD 6 on LH, E₂, and P levels in the mid and late follicular phases.
  
  
  METHODS
  Nested study within a multicenter randomized controlled trial.
  
  
  METHODS
  Reproductive medicine center in an university hospital.
  
  
  METHODS
  One hundred sixty patients undergoing IVF/intracytoplasmic sperm injection (ICSI).
  
  
  METHODS
  Recombinant FSH (150-225 IU) was administered daily from CD 2 onward. The study group (CD 2) started GnRH-a cotreatment on CD 2, whereas the control group (CD 6) started on CD 6.
  
  
  METHODS
  The follicular phase endocrine profile.
  
  
  RESULTS
  The LH levels on CD 6 were lower in the CD 2 group (0.6 ± 0.4 vs. 1.9 ± 1.4 IU/L). The CD 2 group demonstrated both lower E₂ levels on CD 6 (520.1 ± 429.6 pmol/L vs. 1,071.7 ± 654.2 pmol/L) and on the day of hCG administration (3,341.4 ± 1,535.3 pmol/L vs. 4,573.2 ± 2,445.4 pmol/L). The P levels did not differ on CD 6 or on the day of hCG administration.
  
  
  CONCLUSIONS
  Early initiation of GnRH-a cotreatment results in a more stable endocrine profile, with more physiological levels of E2 and LH during the follicular phase. The effect on clinical outcomes must be established in larger trials.
  
  
  BACKGROUND
  NCT00866034.
authors.affiliation: Department of Reproductive Medicine and Gynecology University Medical Centre Utrecht, Utrecht, the Netherlands. O.Hamdine@umcutrecht.nl
authors.forename: Ouijdane
authors.initials: O
authors.lastname: Hamdine
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Broekmans
authors.forename: Marinus J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: Cornelis B
authors.initials: CB
authors.lastname: Lambalk
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
authors.forename: Nick S
authors.initials: NS
authors.lastname: Macklon
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004334:Drug Administration Schedule; D004703:Endocrine System / Q000187:drug effects; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage / Q000494:pharmacology; D005498:Follicular Phase / Q000097:blood / Q000187:drug effects* / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008597:Menstrual Cycle / Q000097:blood / Q000187:drug effects / Q000502:physiology; D010062:Ovulation Induction / Q000379:methods; D011247:Pregnancy; D020554:Sperm Injections, Intracytoplasmic; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005300:Fertility Agents, Female; D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone
keywords: GnRH antagonist; IVF; LH; estradiol; progesterone